Inotropes and Vasopressors Use in Critical Care and Perioperative Medicine: Evidence-Based Approach (Review)

Inotropes and vasopressors are frequently required in critically ill patients and in patients undergoing major surgery. Several molecules are currently available, including catecholamines, phosphodiesterase-3 inhibitors, vasopressin and its analogues, and calcium sensitizers.We will review current evidence on inotropes use in perioperative and critically ill patients, with focus on most recent randomized controlled trials (RCTs).Despite being widely used in anesthesia and intensive care, evidences on safety and efficacy of inotropes are scarce. Data from observational studies suggest that inotropes administration may increase mortality in cardiac surgery, acute heart failure, and cardiogenic shock patients. However, randomized controlled trials did not confirm these findings in acute care settings.Epinephrine has been associated with increased mortality especially in cardiogenic shock, but randomized trials failed to show evidence of increased mortality associated with epinephrine use. Norepinephrine has been traditionally considered contraindicated in patients with ventricular dysfunction, but recent trials suggested hemodynamic effects similar to epinephrine in patients with cardiogenic shock. Dopamine has no additional advantages over norepinephrine and increases the risk of tachyarrhythmias and may increase mortality in cardiogenic shock. Phosphodiesterase-3 (PDE-3) inhibitors are equivalent to catecholamines in terms of major outcomes. Levosimendan is the most investigated inotrope of the last 30 years, but despite promising early studies, high-quality multicenter RCTs repeatedly failed to show any superiority over available agents. There is no highquality RCT clearly demonstrating superiority of one agent over another. In summary, current evidence suggest that the choice of inotrope is unlikely to affect outcome, as long as the target hemodynamic goals are achieved.Finally, in recent years, mechanical circulatory support (MCS) has become increasingly popular. Thanks to improvement in technology, the safety and biocompatibility of devices are constantly growing. MCS devices have theoretical advantages over inotropes, but their use is limited by costs, availability, and invasiveness.Conclusion. Future studies should investigate safety, efficacy, and cost-effectiveness of primary MCS versus primary inotropes in patients with acute cardiovascular failure

Quality of life and satisfaction of patients after oncoplastic or traditional breast-conserving surgery using the BREAST-Q (BCT module): a prospective study

Introduction: The oncoplastic conservative surgery was developed as a natural evolution of traditional surgery, attempting to improve the therapeutic and aesthetic outcomes where tumor resection could be followed by not-adequate results. Our primary aim is to evaluate how patient satisfaction and quality-of-life after conservative oncoplastic surgery, using BREAST-Q (BCT Module), change pre- and post-operatively. The secondary aim is to compare patient-reported outcome after oncoplastic or traditional conservative surgery. Patients and methods: We enrolled 647 patients who underwent traditional conservative surgery or oncoplastic surgery from January 2020 to December 2022. Only 232 women (35.9%) completed the BREAST-Q questionnaire on a web-based platform, at the preoperative phase and 3 months after treatment. Results: The average score of "Psychosocial well-being" and "Satisfaction with Breasts" 3 months after surgery showed a statistically significant improvement, while the average score for "Physical well-being: Chest" at 3 months showed a worsening compared to the baseline. "Sexual well-being" did not show statistically significant change. A significant difference between the post-operative outcome of oncoplastic surgery and traditional surgery was observed only for Physical well-being (better for traditional surgery). Conclusions: The study showed significant improvement in patient-reported outcomes 3 months after the surgery, except for physical discomfort that increases especially after oncoplastic surgery. Furthermore, our data, as well as many others, point to the appropriateness of using OCS where there is an effective indication, while the perspective of patients cannot find significant superiority over TCS in any of the areas analyzed

Guideline-directed medical therapy in severe heart failure with reduced ejection fraction: an analysis from the HELP-HF registry.

AIM: Persistent symptoms despite guideline-directed medical therapy (GDMT) and poor tolerance of GDMT are hallmarks of patients with advanced heart failure (HF) with reduced ejection fraction (HFrEF). However, real-world data on GDMT use, dose, and prognostic implications are lacking. METHODS AND RESULTS: We included 699 consecutive patients with HFrEF and at least one 'I NEED HELP' marker for advanced HF enrolled in a multicentre registry. Beta-blockers (BB) were administered to 574 (82%) patients, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers or angiotensin receptor-neprilysin inhibitors (ACEi/ARB/ARNI) were administered to 381 (55%) patients and 416 (60%) received mineralocorticoid receptor antagonists (MRA). Overall, ≥50% of target doses were reached in 41%, 22%, and 56% of the patients on BB, ACEi/ARB/ARNI and MRA, respectively. Hypotension, bradycardia, kidney dysfunction and hyperkalaemia were the main causes of underprescription and/or underdosing, but up to a half of the patients did not receive target doses for unknown causes (51%, 41%, and 55% for BB, ACEi/ARB/ARNI and MRA, respectively). The proportions of patients receiving BB and ACEi/ARB/ARNI were lower among those fulfilling the 2018 HFA-ESC criteria for advanced HF. Treatment with BB and ACEi/ARB/ARNI were associated with a lower risk of death or HF hospitalizations (adjusted hazard ratio [HR] 0.63, 95% confidence interval [CI] 0.48-0.84, and HR 0.74, 95% CI 0.58-0.95, respectively). CONCLUSIONS: In a large, real-world, contemporary cohort of patients with severe HFrEF, with at least one marker for advanced HF, prescription and uptitration of GDMT remained limited. A significant proportion of patients were undertreated due to unknown reasons suggesting a potential role of clinical inertia either by the prescribing healthcare professional or by the patient. Treatment with BB and ACEi/ARB/ARNI was associated with lower mortality/morbidity

A multi-element psychosocial intervention for early psychosis (GET UP PIANO TRIAL) conducted in a catchment area of 10 million inhabitants: study protocol for a pragmatic cluster randomized controlled trial

Multi-element interventions for first-episode psychosis (FEP) are promising, but have mostly been conducted in non-epidemiologically representative samples, thereby raising the risk of underestimating the complexities involved in treating FEP in 'real-world' services

A Cost-Effective 10-Bit D/A Converter for Digital-Input MOEMS Micromirror Actuation

The design of a 10-bit resistor-string digital-to-analog converter (DAC) for MOEMS micromirror interfacing is addressed in this paper. The proposed DAC, realized in a 0.18-μm BCD technology, features a folded resistor-string stage with a switch matrix and address decoders plus an output voltage buffer stage. The proposed DAC and buffer circuitry are key elements of an innovative scanning micromirror actuator, characterized by direct digital input, full differential driving, and linear response. With respect to the the state-of-the-art resistor-string converters in similar technologies, the proposed DAC has comparable nonlinearity (INL, DNL) performances while it has the advantage of a smaller area occupation, 0.17 mm2, including output buffer, and relatively low-power consumption, 200 μW at 500 kSPS and few μW in idle mode

High-level modeling of resistor string based digital-to-analog converters

To obtain a high performance CMOS resistor string digital-to-analog converter (DAC), one of the key design issues is the mismatch in the resistor ratio. This mismatch causes nonlinearity errors such as integral nonlinearity (INL) and differential nonlinearity (DNL), degrading the performances of the converter. Usually these matching properties are taken into account during the design phase by using time consuming and computational intensive transistor-level Monte Carlo simulations for the process technology corner. Recent research aims at reducing the design time by exploiting high-level modeling of converters as a trade-off between simulation time and modelling accuracy. In this work an analytical model for resistor mismatch in DACs is presented and implemented in MATLAB (TM) environment. The model utilizes geometrical size of resistors and statistical data of the technology process. Starting from random process variations on geometries it was possible to estimate DNL and INL with very short time simulations. The proposed model is valid both for single stage resistor string DACs or segmented ones. The model can be used to speed up the design of resistor-string based DACs, or as a starting point to develop more accurate models by taking into account high-order effects. The model was successfully used to design a 10bit resistor string DAC in a 0.18 mu m BCD technology with DNL and INL lower than 1 LSB (in absolute value). Since the complexity of the DAC is dominated by the resistor string, its optimization since the early design steps, enabled by the proposed high-level model, allowed to minimize area versus state of the art

Efficient test environment for multi-level simulations of mixed-signal systems on chip

The traditional approach for mixed-signal systems is partitioning the design at the beginning of its development cycle: digital and analog portions are then designed and verified separately. The digital design flow is typically top-down, thus allowing a continuous verification of the matching between specification and simulation results. Instead the analog flow is more frequently bottom-up and this makes hard to feedback information from the bottom level simulations to the design top level, being almost impossible SPICE simulations of the whole system (due to the excessive simulation time, convergence troubles and computational effort). This kind of mixed-signal separated flow can easily lead to a final assembly which is not sufficiently tested (such strategy cannot provide the designer with much confidence that digital and analog portions will interface correctly) and thus it's extremely difficult to debug. A full covering test strategy is not allowed also for another reason: many tests are not possible at HDL level, because of the lack of interactivity during simulation process. In fact, if we consider for example a generic calibration sequence, the procedure must assign parameter values depending on DUT state, by changing actions to perform, relating to effects of the previous acted. In this paper we propose a complete environment to test together analog and digital parts by using a semi-automatic VHDL-AMS flow adding the use of Python scripts to drive the simulation, interacting with both Verilog top-level model or real chip, creating a dynamic co-operation for real-time data processing with high re-usability for a fast conditional complete test flow

Bandgap Voltage Reference IC for HV Automotive Applications with Pseudo-regulated Bias and Service Regulator

The paper presents a Bandgap Voltage Reference (BGR) implemented in TSMC 0.25μm BCD technology for an automotive application. To withstand a car’s battery large voltage variations, from 5 V to 40 V, the circuit features an embedded pseudo-regulator providing a stable bias current for the bandgap core. High-voltage (HV) MOS count has been kept low thus allowing the design of a compact BGR with an area of 0.118 mm2. The BGR has been designed to operate in automotive extended temperature range (-40°C to 150°C) and it provides a stable voltage of 1.21 V, which is also used as reference for a cascade 3.7 V linear regulator. Measurements carried on fabricated IC samples prove the effectiveness of the BGR design in terms of supported input voltage variations and operating temperature range, temperature drift, line regulation and PSRR performanc